A new recessive, lethal mutation(nku) with effects on development of the lung and possibly other organs in the mouse is under study. Homozygous mutant newborns die perinatally with atelectatic lungs having the morphological characteristics of 17-18 day fetuses. An initial goal of the proposed research is delineation of all pleiotropic effects of the mutation with particular attention to abnormalities in the lung. Mutant and control animals will be subjected to histological study at the light microscope level and ultrastructural analysis with the electron microscope. A variety of histochemical and biochemical methods (such as analysis of lung phospholipids) will be used to further characterize the specific cellular effects of the nku mutation. In a retrograde study, litters of various gestational ages will be analyzed morphologically and biochemically in order to determine the first temporal or structural aberration during embryonic development. It is hoped that as a result of this investigation, we will understand the mode of action of the nku gene in causing its lethal effects.